OBJECTIVES: Painful diabetic neuropathy (PDN) is a complication of diabetes mellitus. The aim of this research was to describe the epidemiology and economic burden resulting from PDN in Europe. METHODS: A systematic literature review was performed according to a pre-defined search strategy and review criteria in Embase and PubMed from 2003 to 2012. Conference proceedings and Health Technology Assessment (HTA) organizations’ websites were also searched from 2010 to 2012. RESULTS: In total, 23 original studies were identified that covered either epidemiology (n= 16) or economic burden (n=7) for PDN patients in Europe. 13 - 26% of European diabetes patients are reported to develop PDN. Healthcare costs per PDN patient were between €2,441 and €2,963 per annum in UK and Spanish studies, respectively. Inpatient care, medical visits and drug costs accounted for the majority of the total costs, although drug costs can vary widely depending on the choice of medication. Healthcare costs for PDN lead to a high total economic burden for European countries. Considering the identified prevalence data and cost estimates, the estimated total annual healthcare burden for the UK would be approximately €1.7 billion, from a payer perspective. In addition, PDN is significantly associated with disruptions in employment status and productivity loss, primarily driven by impairment while working (presenteeism), resulting in average European per-patient productivity losses of € 10,484 per annum. Pain severity highly influences economic outcomes: higher severity has been linked to significant increases in resource use, productivity losses and healthcare costs. CONCLUSIONS: The large number of PDN patients combined with the cost per patient results in a high economic burden of PDN for European countries. More severe pain results in increased resource use and costs for payers and society; therefore, more effective PDN treatments will lead to patient as well as economic benefits.